Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the alpha2beta1-integrin receptor

Endorepellin, a C-terminal fragment of the vascular basement membrane proteoglycan perlecan, inhibits angiogenesis via the alpha2beta1-integrin receptor. Because this integrin is also implicated in platelet-collagen responses and because endorepellin or its fragments are generated in response to inj...

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Bibliographic Details
Published in:Blood 2007-05, Vol.109 (9), p.3745-3748
Main Authors: Bix, Gregory, Iozzo, Rex A, Woodall, Ben, Burrows, Michelle, McQuillan, Angela, Campbell, Shelly, Fields, Gregg B, Iozzo, Renato V
Format: Article
Language:English
Subjects:
Angiostatic Proteins - metabolism
Angiostatic Proteins - pharmacology
Antibodies - pharmacology
Blood Platelets - cytology
Blood Platelets - metabolism
Cell Membrane - metabolism
Collagen - metabolism
Collagen - pharmacology
Heparan Sulfate Proteoglycans - metabolism
Heparan Sulfate Proteoglycans - pharmacology
Humans
Integrin alpha2beta1 - metabolism
Peptide Fragments - metabolism
Peptide Fragments - pharmacology
Platelet Adhesiveness - drug effects
Platelet Adhesiveness - physiology
Platelet Aggregation - drug effects
Platelet Aggregation - physiology
Protein Structure, Tertiary - physiology
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Summary:Endorepellin, a C-terminal fragment of the vascular basement membrane proteoglycan perlecan, inhibits angiogenesis via the alpha2beta1-integrin receptor. Because this integrin is also implicated in platelet-collagen responses and because endorepellin or its fragments are generated in response to injury and inflammation, we hypothesized that endorepellin could also affect platelet biology. We discovered that endorepellin supported alpha2beta1-dependent platelet adhesion, without appreciably activating or aggregating platelets. Notably, endorepellin enhanced collagen-evoked responses in platelets, in a src kinase-dependent fashion, and enhanced the collagen-inhibitory effect of an alpha2beta1-integrin function-blocking antibody. Collectively, these results suggest that endorepellin/alpha2beta1-integrin interaction and effects are specific and dependent on cell type, differ from those emanated by exposure to collagen, and may be due to cellular differences in alpha2beta1-integrin activation/ligand affinity state. These studies also suggest a heretofore unrecognized role for angiostatic basement membrane fragments in platelet biology.
ISSN:0006-4971